™ © 2022 Blueprint Medicines Corporation

JIM BAKER SVP, Corporate Affairs

INVESTOR DAY 2022 Not for promotional use Our speakers today 3 KATE HAVILAND Chief Executive Officer CHRISTY ROSSI Chief Operating Officer PHILINA LEE, PHD Chief Commercial Officer BECKER HEWES, MD Chief Medical Officer FOUAD NAMOUNI, MD President, R&D PERCY CARTER, PHD Chief Scientific Officer

INVESTOR DAY 2022 Not for promotional use SM, systemic mastocytosis. 4 Agenda Our blueprint to achieve precision at scale Kate Haviland, Chief Executive Officer Delivering the first precision therapy for SM Philina Lee, PhD, Chief Commercial Officer Clinical perspectives on Non-Advanced SM Becker Hewes, MD, Chief Medical Officer Frank Siebenhaar, MD, Assistant Professor, Charité University Pankit Vachhani, MD, Assistant Professor, University of Alabama James Wedner, MD, Professor, Washington Universityin St. Louis BREAK Expanding patient impact with precision medicine leadership Transforming treatment of EGFR-mutant lung cancer Fouad Namouni, MD, President, R&D Research innovation at scale Percy Carter, PhD, Chief Scientific Officer Portfolio growth strategy Christy Rossi, Chief Operating Officer Q&A –Part 2 Closing remarks Kate Haviland, Chief Executive Officer

INVESTOR DAY 2022 Not for promotional use 5 Forward-looking statements Thispresentationcontainsforward-lookingstatementswithinthemeaningofthePrivateSecuritiesLitigationReformActof1995,asamended,including,withoutlimitation,statementsregardingplans, strategies,timelinesandexpectationsforinteractionswiththeU.S.FoodandDrugAdministration(FDA)andotherregulatoryauthorities;planstosubmitasNDAtotheFDAforAYVAKITinnon- advancedSM,withasubsequentsubmissionofatypeIIvariationmarketingauthorizationapplicationtotheEuropeanMedicinesAgency(EMA);plansandtimingforpresentingdetaileddatafromthe PIONEERtrialofAYVAKITinpatientswithnon-advancedsystemicmastocytosis(SM),and,expectationsregardingthepotentialbenefitsofAYVAKITintreatingpatientswithnon-advancedSM; statementsregardingplansandexpectationsforthecompany’scurrentorfutureapproveddrugsanddrugcandidates;thepotentialbenefitsofanyofthecompany’scurrentorfutureapproveddrugs ordrugcandidatesintreatingpatients;andthecompany’sfinancialperformance,strategy,goalsandanticipatedmilestones,businessplansandfocus. Thewords“aim,”“may,”“will,”“could,”“would,”“should,”“expect,”“plan,”“anticipate,”“intend,”“believe,”“estimate,”“predict,”“project,”“potential,”“continue,”“target”andsimilarexpressionsare intendedtoidentifyforward-lookingstatements,althoughnotallforward-lookingstatementscontaintheseidentifyingwords.Anyforward-lookingstatementsinthispressreleasearebasedon management’scurrentexpectationsandbeliefsandaresubjecttoanumberofrisks,uncertaintiesandimportantfactorsthatmaycauseactualeventsorresultstodiffermateriallyfromthose expressedorimpliedbyanyforward-lookingstatementscontainedinthispressrelease,including,withoutlimitation,risksanduncertaintiesrelatedtotheimpactoftheCOVID-19pandemictothe company’sbusiness,operations,strategy,goalsandanticipatedmilestones,includingthecompany’songoingandplannedresearchanddiscoveryactivities,abilitytoconductongoingandplanned clinicaltrials,clinicalsupplyofcurrentorfuturedrugcandidates,commercialsupplyofcurrentorfutureapprovedproducts,andlaunching,marketingandsellingcurrentorfutureapprovedproducts; thecompany’sabilityandplansincontinuingtoestablishandexpandacommercialinfrastructure,andsuccessfullylaunching,marketingandsellingcurrentorfutureapprovedproducts;the company’sabilitytosuccessfullyexpandtheapprovedindicationsforAYVAKIT/AYVAKYTandGAVRETOorobtainmarketingapprovalforAYVAKIT/AYVAKYTinadditionalgeographiesinthefuture; thedelayofanycurrentorplannedclinicaltrialsorthedevelopmentofthecompany’scurrentorfuturedrugcandidates;thecompany’sadvancementofmultipleearly-stageefforts;thecompany’s abilitytosuccessfullydemonstratethesafetyandefficacyofitsdrugcandidatesandgainapprovalofitsdrugcandidatesonatimelybasis,ifatall;thepreclinicalandclinicalresultsforthecompany’s drugcandidates,whichmaynotsupportfurtherdevelopmentofsuchdrugcandidateseitherasmonotherapiesorincombinationwithotheragentsormayimpacttheanticipatedtimingofdataor regulatorysubmissions;thetimingoftheinitiationofclinicaltrialsandtrialcohortsatclinicaltrialsitesandpatientenrollmentrates;actionsofregulatoryagencies,whichmayaffecttheinitiation, timingandprogressofclinicaltrials;thecompany’sabilitytoobtain,maintainandenforcepatentandotherintellectualpropertyprotectionforAYVAKIT/AYVAKYT,GAVRETOoranydrugcandidatesit isdeveloping;thecompany’sabilitytodevelopandcommercializecompaniondiagnostictestsforAYVAKIT/AYVAKYT,GAVRETOoranyofitscurrentandfuturedrugcandidates;thecompany’sability tosuccessfullyexpanditsoperations,researchplatformandportfoliooftherapeuticcandidates,andthetimingandcoststhereof;thecompany’sabilitytorealizetheanticipatedbenefitsofits executiveleadershiptransitionplan;andthesuccessofthecompany’scurrentandfuturecollaborations,financingarrangements,partnershipsorlicensingarrangements.Theseandotherrisksand uncertaintiesaredescribedingreaterdetailinthesectionentitled“RiskFactors”inthecompany’sfilingswiththeSecuritiesandExchangeCommission(SEC),includingthecompany’smostrecent AnnualReportonForm10-K,assupplementedbyitsmostrecentQuarterlyReportonForm10-QandanyotherfilingsthatthecompanyhasmadeormaymakewiththeSECinthefuture.The forward-lookingstatementsinthispresentationaremadeonlyasofthedatehereof,andexceptasrequiredbylaw,thecompanyundertakesnoobligationtoupdateanyforward-lookingstatements containedinthispresentationasaresultofnewinformation,futureeventsorotherwise.Accordingly,readersarecautionednottoplaceunduerelianceontheseforward-lookingstatements. Thispresentationalsocontainsestimates,projectionsandotherstatisticaldatamadebyindependentpartiesandbythecompanyrelatingtomarketsizeandgrowthandotherdataaboutthe company'sindustry.Thesedatainvolveanumberofassumptionsandlimitations,andyouarecautionednottogiveundueweighttosuchestimates.Inaddition,projections,assumptionsand estimatesofthecompany'sfutureperformanceandthefutureperformanceofthemarketsinwhichthecompanyoperatesarenecessarilysubjecttoahighdegreeofuncertaintyandrisk. BlueprintMedicines,AYVAKIT,AYVAKYT,GAVRETOandassociatedlogosaretrademarksofBlueprintMedicinesCorporation.

INVESTOR DAY 2022 Not for promotional use Our blueprint to achieve precision at scale Chief Executive Officer KATE HAVILAND

INVESTOR DAY 2022 Not for promotional use OUR MISSION Make real the promise of precision therapy to extend and improve life for as many people as possible Not for promotional use Suki, patient with non-advanced systemic mastocytosis

INVESTOR DAY 2022 Not for promotional use Blueprint’s proven track record of success FDA, U.S. Food and Drug Administration; IND, investigational new drug application; POC, proof-of-concept. development candidates nominated breakthrough therapy designations success rate from IND to clinical POC 14 80% 5 years from IND to first approval FDA approved indications approved medicines ~4 25 8

INVESTOR DAY 2022 Not for promotional use 9 Our evolution to a commercial stage company Compelling peak revenue and high margin opportunities leveraging operational efficiencies People, tools and capabilities to capture the compelling growth opportunities Sustainable disease leadership in Systemic Mastocytosis through a decade of research, relationships and market building OPPORTUNITY INFRASTRUCTURE KNOWLEDGE & EXPERIENCE

INVESTOR DAY 2022 Not for promotional use Our commercial portfolio creates value certainty and opportunity for near-term growth 10 AREA PDGFRA GIST RET-altered cancers Advanced SM Non-Advanced SM GLOBAL TAMs PRODUCTS Anticipated Approval Mid-2023 ~12,000 patients 2 marketed products GIST, gastrointestinal stromal tumor; TAM, total addressable market (US, EU4 and UK markets). Total revenue and operating expenses favorable to consensus Expect to achieve high-end of $180M -$200M top-line revenue guidance for 2022 Revising AYVAKIT revenue guidance to $108 million to $111 million for 2022 Q3 financial results

INVESTOR DAY 2022 Not for promotional use Patient impact and growth driven by Precision at Scale 11 LUNG CANCER PORTFOLIO BLU-222 AREA PDGFRA GIST RET-altered cancers Advanced SM Non-Advanced SM* EGFRm NSCLC* CDK2 vulnerable breast & other cancers* GLOBAL TAMs PRODUCTS ~250,000+ patients 4+ marketed products by the end of 2027 CDK2, cylindependent kinase 2; EGFRm, EGFR-mutant; NSCLC, non-small cell lung cancer. * Includes TAMs for AYVAKIT based on potential approval in Non-Advanced SM and other investigational therapies based on potential future approvals in other target indications.

INVESTOR DAY 2022 Not for promotional use 12 “2027 Blueprint” strategy -double our impact, in half the time Approved medicines Disease leadership areas Late-stage clinical programs Research platforms Cumulative development candidates 2011-2022 2 1 2 1 14 Planned 2022-2027 4+ 3+ 4+ 2 25+ 2027

INVESTOR DAY 2022 Not for promotional use Key questions to be answered today 13 What is the opportunity in Non-Advanced SM and how does our Advanced SM experience inform our view? EXPANDING PATIENT IMPACT SOLVING MAJOR MEDICAL PROBLEMS SCALING INNOVATION Do we have a winning approach to improve outcomes for patients with EGFR-mutant NSCLC? How will we leverage our expertise and infrastructure to drive continued innovation and long-term growth?

INVESTOR DAY 2022 Not for promotional use Precision at Scale: Bringing AYVAKIT to patients across the spectrum of systemic mastocytosis 14 What is the opportunity in Non-Advanced SM and how does our Advanced SM experience inform our view? EXPANDING PATIENT IMPACT 1 2 3 Growing the number of Advanced SM patients treated with AYVAKIT each quarter and addressing challengesin underpenetrated patient populations Expanding AYVAKIT to treat patients with Non-Advanced SM is a significant opportunity for near-term growth PIONEER data establish the basis for AYVAKIT to become the standard of care for patients with moderate-to-severe Non-Advanced SM upon FDA approval

INVESTOR DAY 2022 Not for promotional use Precision at Scale: Delivering improved outcomes for people withEGFR-mutant NSCLC 15 SOLVING MAJOR MEDICAL PROBLEMS Do we have a winning approach to improve outcomes for patients with EGFR-mutant NSCLC? 1 2 3 4 BLU-945 monotherapy was clinically active and showed adifferentiated safety profile. However, durability of response was limited due to frequent off-target drivers in 2L+ patients Pulling forward BLU-525, the backup compound for BLU-701, to bring the best candidate into development with minimal disruption to the overall timeline Encouraging early activity data from the BLU-451 dose escalation trial Prioritizing development of BLU-945 in combination with osimertinibin 1L L858R, based on exciting preclinical data and early clinical safety data 1L, first-line; 2L+, second-line or later.

INVESTOR DAY 2022 Not for promotional use Precision at Scale: Driving innovation for long-term growth 16 How will we leverage our expertise and infrastructure to drive continued innovation and long-term growth? SCALING INNOVATION 1 2 3 Creating synergies between our robust discovery, clinical and commercial capabilities to build an optimized portfolio Announcing a new program targeting wild-type KIT, which builds on ourknowledge of KIT and leadership position in mast cell disorders Leveraging our kinase discovery platform as a unique advantage to pursue targeted protein degradation

INVESTOR DAY 2022 Not for promotional use Delivering the first precision therapy for systemic mastocytosis Chief Commercial Officer PHILINA LEE, PHD

INVESTOR DAY 2022 Not for promotional use OUR MISSION Make real the promise of precision therapy to extend and improve life for as many people as possible Not for promotional use Melanie, patient with non-advanced systemic mastocytosis

INVESTOR DAY 2022 Not for promotional use 19 AYVAKIT is the first precision therapy to target the underlying cause of SM Reduced mast cell burden Improved disease symptoms Improved quality of life Deep and durable clinical responses Positive benefit-risk profile COMPELLING PROFILE DEMONSTRATED ACROSS CLINICAL TRIALS One pill, once daily dosing

INVESTOR DAY 2022 Not for promotional use 20 We are well positioned to deliver on the promise of AYVAKIT in SM AYVAKIT has the potential to benefit patients across the spectrum of SM • This represents a >$1B opportunity We have established AYVAKIT as the standard of care for patients treated for AdvSM • Focused on increasing the treated patient population to drive near-term growth Our Non-AdvSMU.S. launch strategy focuses on ~7,500 patients with moderate to severe disease who are seeking treatment today We are well-positioned to launch AYVAKIT for Non-AdvSM • First to market, a strong product profile, a leadership position built over nearly a decade, and an experienced team in the market today for AdvSM AdvSM, Advanced SM; Non-AdvSM, Non-Advanced SM.

INVESTOR DAY 2022 Not for promotional use Systemic mastocytosisrepresents a blockbuster opportunity 21 ~550 patients ~2,100 patients ~7,500 patients 1 Advanced SM treated 2 Advanced SM untreated 3 Moderate-to-severe non-advanced SM diagnosed & treated 4 Additional opportunity SM PATIENTS IN THE U.S. ~32,000 estimated prevalent patients based on epidemiology data 2 ~16,000 patients diagnosed and observable in claims data 1 ~6,000 other diagnosed non-advanced SM ~16,000 undiagnosed SM (not visible in claims) ~22,000 patients 1. U.S. claims data analyses on file. 2. Cohen, Br J Haematol, 2014.

INVESTOR DAY 2022 Not for promotional use Systemic mastocytosisis a spectrum of disease AHN, associated hematologic neoplasm. 22 ADVSM(5-10%) ADVSM(5-10%) NON-ADVSM(90-95%) NON-ADVSM(90-95%) •Mast cell proliferationleads to organ damage and shortened overall survival •Managed primarily by hematologist oncologists whose treatment goals are focused on overall survival •Three sub-types of disease create significantheterogeneity; majority of patients haveSM-AHN, a medically complex disease •Mast cell over-activationleads to debilitating symptoms and poor quality of life •Managed primarily byhematologist oncologists, as well as allergist immunologists who are focused on symptom burden and quality of life •More homogenous disease biology, with a range of clinical presentations leading to a spectrum of severity SYSTEMIC MASTOCYTOSIS ~32K prevalent patients, with ~16K diagnosed and visible in U.S. claims

INVESTOR DAY 2022 Not for promotional use AYVAKIT has become the standard of care in treated AdvSMin the U.S. 23 ~550 patients ~2,100 patients 1 Advanced SM treated 2 Advanced SM untreated 3 Moderate-to-severe non-advanced SM diagnosed & treated 4 Additional opportunity GROWTH OPPORTUNITY Continue to expand the treated advanced SM population ~4x

INVESTOR DAY 2022 Not for promotional use 24 Growth in AYVAKIT revenue one year into the Advanced SM launch •AVYAKIT is the standard of care in the U.S. ‒~60% share of treated patients in Q3 ‒~75% of new patient starts / switches ‒Number of patients on therapy continues to grow •Increasing HCP experience with AYVAKIT ‒~350 new accounts since launch ‒>50 new accounts in Q3 KEY CHALLENGES KEY DRIVERS •Initial penetration in SM-AHN is lower than other subtypes •Omicron COVID-19 impacted patient visits and new patient diagnoses •FX headwinds in international business $14.7 $18.0 $21.3 $24.7 $25.1 $2.6 $2.0 $2.5 $3.8 $3.6 Q3 2021Q4 2021Q1 2022Q2 2022Q3 2022 $17.3M $20.0M $23.8M $28.5M $28.6M QUARTER OVER QUARTER GROWTH ~ +65% U.S.Rest of world 1 FX, foreign exchange. 1. Rest of world sales exclude Greater China.

INVESTOR DAY 2022 Not for promotional use 25 Trending to double AYVAKIT net product revenues compared to last year •Updating AYVAKIT net product revenue guidance for full-year 2022 to $108M -$111M, based on: •Continued expected growth of treated patients at a slower pace, driven by expansion ofSM-AHN treatment rates •Financial impacts driven by FX and German price reform •Reasons to believe in continued growth •Total number of patients on therapy continues to grow •Majority of SM-AHN anticipated to be addressable over time •Duration of treatment continues to trend favorably (~18 months), trending towards longer duration in recently prescribed patients, who are primarily TKI-naïve FY 2021 (actual)FY 2022 (expected) YEAR OVER YEAR GROWTH ~ +2x Global Net Revenues $53.0M $108-$111M TKI, tyrosine kinase inhibitor.

INVESTOR DAY 2022 Not for promotional use 26 We are taking action to drive change in AdvSMclinical practice HCP education , including peer-to-peer, on SM-AHN and urgency to treat Real-time data alerts to field, enhanced by machine learning, to flag patients most likely to start therapy Additional data generation , including impact of long-term treatment and data on combination approaches Incremental field team expansion, ahead of anticipated NonAdvSMlaunch, will broaden our reach to call on additional providers treating AdvSMpatients HCP, healthcare provider;

INVESTOR DAY 2022 Not for promotional use A 20% subset of SM patients identified though AI / machine learning approaches generates ~80% of new SM-directed TKI starts Patient-level data alerts enable highly targeted HCP engagement by field teams = SM patient initiating a TKI or cytoreductive therapy 27 Key initiatives to grow the treated AdvSMpatient population 46.9 mos (95%CI: 44.9,NE) 18.0 mos (95%CI: 13.0, 26.8) INITIATIVE 1: EDUCATING HCPsON URGENCY TO TREAT INITIATIVE 2: INCREASING FIELD EFFICIENCY WITH AI/MACHINE LEARNING 1. A multi-center, global, observational, retrospective chart review study was conducted at 6 study sites (4 European, 2 US) to identify and collect data from AdvSMpatients who received BAT. SM- AHN patients were identified using inclusion/exclusion criteria similar to the EXPLORER and PATHFINDER trials. The follow-up times for the midostaurin, cladribine, and BAT cohorts were truncated to match the maximum follow-up time of the avaprtinibcohort. Reiter et al. Overall Survival in Patients with Systemic Mastocytosiswith Associated Hematologic Neoplasm Treated with Avapritinib Versus Best Available Therapy. Presented at EHA 2022. BAT, best available therapy. AI, artificial intelligence. AYVAKIT improved OS in SM-AHN patients compared to best available therapy in a retrospective analysis. 1 In October, NCCN guidelines for SM were updated to cite these study results.

INVESTOR DAY 2022 Not for promotional use Non-advanced SM is a significant opportunity with high growth potential 28 ~550 patients 1 Advanced SM treated 2 Advanced SM untreated 4 Additional opportunity GROWTH OPPORTUNITY ~7,500 patients with moderate-to-severe Non-AdvSMalready diagnosed and treated today ~15x ~7,500 patients 3 Moderate-to-severe non-advanced SM diagnosed & treated

INVESTOR DAY 2022 Not for promotional use GROWTH OPPORTUNITY EARLIEST ADOPTION Our U.S. launch strategy focuses on addressing the needs of ~7,500 patients U.S. claims data analyses on file. Rx, prescription. 29 ~2,500 severe ~5,000 moderate ~7,500 patients diagnosed with moderate-to-severe Non-AdvSM, treated with symptom- directed polypharmacy •Higher burden of disease (e.g., higher frequency of anaphylaxis, organomegaly, compromised bone) •Polypharmacy burden includes higher utilization of TKIs, cytoreductive therapies, and omalizumab •Moderate burden of disease •Polypharmacy burden includes long-term use of steroids, cromolyn sodium or Rx antihistamines

INVESTOR DAY 2022 Not for promotional use 30 Claims data illustrate disease burden and informs field targeting 1. Claims algorithm considers number & type of SM diagnosis codes, comorbidities including associated hematologic neoplasms (AHNs) and evidence of organ damage (e.g., splenomegaly, hepatomegaly, compromised bone, etc.), in addition to prescription therapies (e.g., trial of TKIs / cytoreductive therapies, cromolyn sodium, long-term steroid use, omalizumab, epi-pen, etc.). CM, cutaneous mastocytosis; ISM, indolent systemic mastocytosis. Both medical and pharmacy claims are captured. Advanced SM Patient Severe Non-Advanced SM Patient OtherDiagnosed Non-Advanced SM Patient Moderate Non-Advanced SM Patient 1 2 3 4 ICD-10 Diagnosis Code Used in Encounter: Systemic Mastocytosis (D4702) Aggressive SM (C9621) Cutaneous Mastocytosis (D4701) Other Events Emergency Room Visit EpiPen Rx SM-directed Symptomatic Rx Omalizumab Rx Other / None Claims-based patient journeys for representative patients:

INVESTOR DAY 2022 Not for promotional use Engage top treaters to raise awareness of SM and need for treatment Educate and empower patients to seek support Launch strategy to drive continued growth in Non-Advanced SM 31 PREPARE LAUNCH ACCELERATE GROW Activate HCPs managing large numbers of patients Use data publications and presentations to inform and educate Ensure patient access Encourage coordination among a broader set of HCP specialties to accelerate uptake across segments Grow the market by driving an increase in diagnosis via awareness and testing Support development of SM Centers of Excellence TODAY2H 20232024 2025+

INVESTOR DAY 2022 Not for promotional use U.S. claims data on file. AI, allergist immunologist; derm, dermatologist; heme/onc, hematologist oncologist; GI, gastroenterologist. 32 Analytics based on provider segmentation enables efficient, targeted outreach Top 350+ HCPs see ~1.5K patients +3K HCPs see ~2K patients +4K HCPs see ~4K patients HEME/ONC& AI GI, DERM& OTHER # treating physicians managing ~7,500 moderate to severe Non-AdvSMpatients # SM patients managed Figure is illustrative

INVESTOR DAY 2022 Not for promotional use Favorable access to AYVAKIT today provides a strong foundation DOSES AVAILABLE TODAY100% PAYER COVERAGERAPID TIME TO FILL All doses approved for AdvSM and GIST, including the 25mg dose, are available and covered by payers 100% payer coverage for all AYVAKIT NDCs, including 25mg 1 AYVAKIT sees rapid time to fill and payer prior authorization approvals Average Days to Fill* 4.9 Average Days to PA Approval* 2.6 AVYAKIT AdvSMCoverage, by Percentage of Lives Coverage to label, 97% Confirmed coverage, 100% 25 mg 50 mg 100 mg 200mg 300mg Expect strong access for Non-Advanced SM at launch based on rare disease profile, significant medical need, and lack of approved treatments 33 *September 2022, prior 90-day lookback period. 1. Market research data on file, Complete Market Payer Research Conducted in September, 2022. NDC, national drug code. PA, priorauthorization. Coverage requires prescribing by specialists and/or KIT D816V testing, 3%

INVESTOR DAY 2022 Not for promotional use 34 Patient support streamlines the access process for patients SUPPORT OFFERED 1 Minimizes out-of- pocket cost burden for patients 2 Streamlines the access process for patients 3 Provides ongoing information and support to enable adherence PATIENT SUPPORT MODEL Copay Assistance* Patient Assistance Program QuickStart Coverage Interruption Reimbursement Support Resources Dose Exchange Nearly half of patients receiving AYVAKIT have enrolled in YourBlueprint, exceeding industry benchmarks * For eligible patients.

INVESTOR DAY 2022 Not for promotional use An educated patient can be a catalyst for disease treatment 35 WEBSITE SOCIAL It’s SM thingpatient and caregiver education campaign First launched in Q1 2022 ~7K patients and caregivers have opted in for routine engagement ~1.3K downloads of a doctor discussion guide High interest in HCP and patient ambassador webinar series (started in Q3) Patient education efforts amplified by long-standing, committed partnerships with patient advocacy groups

INVESTOR DAY 2022 Not for promotional use Breadth of opportunity to drive long-term AYVAKIT growth 36 1 Advanced SM treated 2 Advanced SM untreated 3 Moderate-to-severe non-advanced SM diagnosed and treated 4 Additional opportunity ~6,000 other diagnosed non-advancedSM ~16,000 undiagnosed SM (not visible in claims) ~22,000 patients 1. U.S. claims data analyses on file. 2. Cohen, Br J Haematol, 2014. GROWTH OPPORTUNITIES Increase diagnosis of SM with education and testing Broaden reach to spectrum of non-advanced SM

INVESTOR DAY 2022 Not for promotional use U.S. claims data analyses on file. 37 Our efforts with the SM community have grown the number of diagnosed patients Q2 Q1 2019 Q2Q4Q1 2020 Q1 2022 Q2Q3Q3 Q4Q1 2021 Q4Q2 Q3 Jan’20: AYVAKIT approved for PDGFRA GIST PREVALENT SM PATIENTS OBSERVED IN US CLAIMS DATA Jun’21: AYVAKIT approved for Advanced SM 70%

INVESTOR DAY 2022 Not for promotional use 38 We are well positioned to deliver on the promise of AYVAKIT in SM AYVAKIT has the potential to benefit patients across the spectrum of SM • This represents a >$1B opportunity We have established AYVAKIT as the standard of care for patients treated for AdvSM • Focused on increasing the treated patient population to drive near-term growth Our Non-AdvSMU.S. launch strategy focuses on ~7,500 patients with moderate to severe disease who are seeking treatment today We are well-positioned to launch AYVAKIT for Non-AdvSM • First to market, a strong product profile, a leadership position built over nearly a decade, and an experienced team in the market today for AdvSM.

INVESTOR DAY 2022 Not for promotional use Clinical perspectives on non-advanced SM Chief Medical Officer BECKER HEWES, MD

INVESTOR DAY 2022 Not for promotional use Uncontrolled mast cell proliferation and activation in Non-Advanced SM causes severe and unpredictable symptoms across multiple organ systems 1-3 40 Syncope, dizziness, palpitations, Hypotensive anaphylaxis Diarrhea, nausea/vomiting, painBone/muscle pain, osteoporosis Darier’s sign, dermatographism, extreme flushing, pruritus Brain fog, depression, migraines, anxiety Elsaiey, A, et al. Mastocytosis-A Review of Disease Spectrum with Imaging Correlation. Cancers .. 2021; 13(20):5102. Boddaert, N et al. Neuroimaging evidence of brain abnormalities in mastocytosis. Translational Psychiatry 2017; 7, e1197 Berezowska, S., et al. Adult-onset mastocytosisin the skin is highly suggestive of systemic mastocytosis. Mod Pathol 2014;27,19–29. Dyspnea, congestion, throat swelling, wheezing D816V Mast cells MUSCULOSKELETAL RESPIRATORY SKIN NEUROPSYCHIATRIC CARDIOVASCULAR GASTROINTESTINAL SYSTEMIC fatigue, malaise, weight loss

INVESTOR DAY 2022 Not for promotional use 41 THE FIRST STUDY TO SHOW DISEASE MODIFICATION AND BENEFIT IN INDOLENT SYSTEMIC MASTOCYTOSIS

INVESTOR DAY 2022 Not for promotional use PIONEER: Largest clinical trial in Non-Advanced SM Data cutoff as of June 23, 2022. QD, once daily; BSC, best supportive care; QD, once daily; SD, standard deviation. 42 PART 1: DOSE-FINDING AYVAKIT 25 mg QD + BSC AYVAKIT 50 mg QD + BSC AYVAKIT 100 mg QD + BSC Placebo QD + BSC Select Dose Randomize 1:1:1:1 AYVAKIT 25 mg QD + BSC AYVAKIT 25 mg QD + BSC Placebo QD + BSC PART 2: PIVOTAL EFFICACY Rollover Endpoint Randomize 2:1 24 weeks Today’s Topics 1 2 3 INTERPRETATION OF THE STUDY RESULTS PHYSICIAN INTERPRETATION OF THE DATA WHEN WILL WE GET MORE DATA? •Clinical meaningfulness •Decision to prescribe if approved •Dose selection •Patient selection •Placebo performance

INVESTOR DAY 2022 Not for promotional use AYVAKIT demonstrated highly significant and clinically meaningful impact Data cutoff as of June 23, 2022. 1. One-sided p-value < 0.025 indicates statistical significance. 2. For secondary endpoints, reductions in TSS and objective measures of mast cell burden represent proportion of patients with ≥30% and ≥50% reductions. All endpoints are key secondary endpoints, except for “Mean Change in Most Severe Symptom Score”, which is an additional secondary endpoint. TSS, total symptom score; VAF, variant allele fraction; MC, mast cell. 43 Primary Endpoint Mean Change in TSS 0.003 Secondary Endpoints 2 ≥30% Reduction in TSS 0.009 ≥50% Reduction in TSS 0.005 Mean Change in Most Severe Symptom Score 0.015 ≥50% Reduction in Serum Tryptase <0.0001 ≥50% Reduction in KIT D816V VAF <0.0001 ≥50% Reduction in Bone Marrow MC Aggregates <0.0001 P VALUE 1 CLINICAL OUTCOME MEASURES

INVESTOR DAY 2022 Not for promotional use Data cutoff as of June 23, 2022. CI, confidence interval; SD, standard deviation AYVAKIT decreased patient-reported symptoms and objective measures of disease burden PART 2: PRIMARY ENDPOINT Mean change in Total Symptom Score (TSS) [95% CI] AYVAKIT -20.2 [-24.7 –-15.7] AYVAKIT Control 53.9% [45.3 –62.3] 0.0% [0.0 –5.1] PART 2: SECONDARY ENDPOINT Proportion of patients with ≥50% reduction in serum tryptase [95% CI] week 24 week 48 AYVAKIT Control -15.6 [-18.6 –-12.6] -9.2 [-13.1 –-5.2] week 24 44 rollover

INVESTOR DAY 2022 Not for promotional use AYVAKIT was well-tolerated with a safety profile favorable to control Data cutoff as of June 23, 2022. 1. Cognitive effect AEs refer to 17 pooled terms identified across AYVAKIT clinical studies.AE, adverse event; ICB, intracranial bleed; SAE, serious adverse event; TRAE, treatment-related adverse event. 45 AYVAKIT Control AEs, n (%)128 (90.8)66 (93.0) SAEs, n (%)7 (5.0)8 (11.3) Discontinuation due to TRAEs, n (%)1 (0.7)0 (0.0) TRAEs in ≥5% of AYVAKIT patients, by preferred term Headache, n (%) 11 (7.8)7 (9.9) Nausea, n (%) 9 (6.4)6 (8.5) Peripheral edema, n (%)9 (6.4)1 (1.4) Periorbital edema, n (%)9 (6.4)2 (2.8) •No ICB events •Lower rate of cognitive effect AEs 1 reported for AYVAKIT (2.8%) vs. control (4.2%) •No Grade 3 cognitive effect AEs 1 for AYVAKIT (0%) vs. control (1.4%) •In the AYVAKIT arm, 93% of edema AEs were Grade 1, with remainder Grade 2 •Higher Part 2 completion rate for AYVAKIT (96.5%) vs. control (93.0%)

INVESTOR DAY 2022 Not for promotional use * >50 ng/ml at baseline. TSS, total symptom score. 46 Maximum symptom improvement seen with 25 mg irrespective of tryptase reduction Part 1 Part 2 ****** -100% -50% 0% 50% 100% 25mg (n=10) 50 mg (n=10) 100 mg (n=10) * no data available Placebo (n=9) % CHANGE IN SERUM TRYPTASE FROM BASELINE week 24 TSS REDUCTION FROM BASELINE week 24 • DEEP SYMPTOM REDUCTION • SYMPTOM REDUCTIONWAS NOT CORRELATED WITH TRYPTASE REDUCTION Comparison of % change in TSS & % change in tryptase Low Correlation Coefficient 0.38 -25 -20 -15 -10 -5 0 Placebo25mg50mg100mg Patients with High Baseline Tryptase*

INVESTOR DAY 2022 Not for promotional use Health State Mobility Self- Care Usual Activities Pain / Discomfort Anxiety / Depression NON-ADVANCED SM PATIENT QOL IS LOWER THAN SOME TERMINAL DISEASES AYVAKIT LED TO CLINICALLY MEANINGFUL INCREASES IN QOL AT 24 WEEKS QOL, Quality of Life 1. Average EQ-5D score of all PIONEER patients at baseline; 2. Jiang R, et al., Qual Life Research. 2021;30; 3. Pickard AS, et al., Qual Life Outcomes. 2007. Non-Advanced SM patients had poor QoL and improved on AYVAKIT EQ-5D IS A WIDELY-USED QOL TOOL PIONEER Trial 0.0 0.2 0.4 0.6 0.8 1.0 U.S. general population 2 Non- Advanced SM 1 Lung Cancer Acute Intermittent Porphyria 3.20% 11.30% Placebo AYVAKIT (Mean change, %) 47

INVESTOR DAY 2022 Not for promotional use AYVAKIT showed reduction in polypharmacy: illustrative example oral cromolyn Anti-IgE, anti-immunoglobulin E; NSAIDS, non-steroidal anti-inflammatory drugs. 48 MEDICATION CLASSES MULTIPLE SYMPTOMS H1 inhibitors H2 inhibitors Leukotriene inhibitors Systemic steroids Anti-IgEantibodies GASTROINTESTINAL Proton Pump Inhibitors Oral Cromolyn Anti-diarrheals ANAPHYLAXIS EpiPens OSTEOPOROSIS Bisphosphonates PAIN NSAIDS Opiates ORAL CROMOLYN SODIUM • High concentration oral formulation of cromolyn sodium • Recommended dose 2 vials diluted in water 4x day, before meals and at bedtime PIONEER • 58 patients used at baseline 13/58 (22%) 0/31 (0%) AYVAKIT 25 mg QD + BSC Placebo QD + BSC (Control) Patients who reduced their dose or frequency of taking oral cromolyn sodium by month 6

CASE PRESENTATIONS & PANEL DISCUSSION Assistant Professor of Medicine Hematology Oncology University of Alabama School of Medicine Birmingham, Alabama Pioneer Investigator PANKITVACHHANI, MD Professor of Medicine Division of Allergy and Immunology Washington University St. Louis, Missouri H. JAMES WEDNER, MD Assistant Professor Head IFA Outpatient Clinic for Allergology Charité University Berlin, Germany Pioneer Investigator FRANK SIEBENHAAR, MD Drs. Vachhani, Wedner and Siebenhaar have consulting relationships with Blueprint Medicines

INVESTOR DAY 2022 Not for promotional use BASELINE SYMPTOMOLOGY 50 Case 1 –Prof. Siebenhaar GI : recurrent, unpredictable diarrhea Neuro: Brain fog, dizziness, headache Skin : lesions < 60%; triggered by exercise, shower, hot bath Skeletal: Bone pain 34-year-old man •Allergic rhinitis, asthma in 1990 • Diagnosed @ 20yrs old –non-advanced SM in 2008 •KIT D816V positive •Baseline tryptase < 20ng/ml •Ebastine(H1-blocker) •Famotidine •Cromoglycate •Epipen PATIENT JOURNEY POLYPHARMACY PATIENT ADOPTED LIFESTYLE TO SYMPTOMS Forgot what “normal” felt like Working from home, fatigue

INVESTOR DAY 2022 Not for promotional use 1. Jiang R, et al., Qual Life Research. 2021;30. ISM, indolent SM; MC-QOL, mastocytosisquality of life questionnaire. 51 Case 1 –Symptom & QoL improvement after 6 months AYVAKIT treatment Emotions Skin Social Life/ Functioning Symptoms Total Score MC-QOL (lower = health improvement) avapritinib25 mg @ 24 weeks Baseline EQ-5D (higher = health improvement) U.S. General Population 1 +42% ISM – SYMPTOM ASSESSMENT FORM (lower = health improvement) fatigue brain fog flushing spots bone pain itching headache abdominal pain dizziness nausea diarrhea Total Symptom Score

INVESTOR DAY 2022 Not for promotional use 52 Case 1 –Symptoms and overall improvements SKIN IMPROVEMENTS Before After • Patient reports “life-changing” improvement , including continued improvement in QoL – Ability to be more productive at work •No new symptoms, and reduction in skin and GI symptoms •No diarrhea after 6 months THIS PATIENT REMAINS ON AYVAKIT TODAY BeforeAfter AYVAKIT OUTCOMES Patients’ permission granted for use of photos. GI, gastrointestinal.

INVESTOR DAY 2022 Not for promotional use BASELINE SYMPTOMOLOGY 53 Case 2 –Dr. Vachhani GI : Chronic diarrhea, pain with food Neuro: Brain fog Skin : Typical SM lesions on trunk and limbs Skeletal: Bone Pain Systemic: Recurrent anaphylaxis, flushing 39-year-old mother of four •First symptoms in 2017 • Diagnosed @ 36 yrsold –non-advanced SM in 2019 •KIT D816V positive •Prior midostaurin, interferon, IV famotidine •Baseline tryptase < 20ng/ml •Oral cromolyn •famotidine •levocertrizine •fexofenadine •omalizumab •doxepin •montelukast (others) • Epipen(99 in one year) PATIENT JOURNEY POLYPHARMACY PATIENT ADOPTED LIFESTYLE TO SYMPTOMS Had to isolate, wear N95 mask in pubic before COVID pandemic Stopped working and traveling Unable to attend kids’ events Multiple episodes of life-threatening anaphylaxis

INVESTOR DAY 2022 Not for promotional use 1. Jiang R, et al., Qual Life Research. 2021;30 54 Case 2 –Quality of life improvements avapritinib25mg Week 19 Baseline Emotions Skin Social Life/ Functioning Symptoms Total Score +38% U.S. General Population 1 MC-QOL (lower = health improvement) EQ-5D (higher = health improvement) ISM – SYMPTOM ASSESSMENT FORM (lower = health improvement) Baseline fatigue brain fog flushing spots bone pain itching headache abdominal pain nausea diarrhea Total Symptom Score dizziness avapritinib25mg Week 23

INVESTOR DAY 2022 Not for promotional use Dr. Wedner’sPractice –Washington University Division of Allergy & Immunology Systemic Mastocytosis Practice • Treats multiple disorders including HAE, resistant atopic diseases, & routine allergy disorders • Currently ~50 patients with SM ‒ ~5-10 advanced SM ‒ ~20 very bad/debilitating ‒ ~20 significant disease Referral basis • ER anaphylaxis patients • Allergists • Dermatologists –hives and skin lesions, dermatographism • Gastroenterologists –diarrhea and GI pain • Neuro –unexplained brain fog Referral Region 55 ER, emergency room; HAE, hereditary angioedema.

INVESTOR DAY 2022 Not for promotional use 56 Case Study #3 –Dr. Wedner 41-year-old woman •Referred by local ER for anaphylaxis • GI : Frequent stomach upset • Skin : Years of itching and skin flushing • Systemic: Occasional shortness of breath Polypharmacy Additional History & Testing Presentation •Certrizine •Famotidine •Montelukast •Zyflo CR •Ketotifen •Gastrocrom •EpiPen • Skin: spots, severe flushing episodes • GI: Nausea, vomiting & frequent diarrhea “Food allergy?” •Darier’s Sign on Physical Exam •Osteopenia •Tryptase = 42 •ddPCR–D816V pos •Marrow mast cells CURRENT SYMPTOMS Persistent GI symptoms Episodic flushing and itching Anxiety about anaphylaxis Spots ddPCR, digital droplet polymerase chain reaction.

INVESTOR DAY 2022 Not for promotional use 57 A new era for patients with Systemic Mastocytosis Non-Advanced SM is a devastating disease without any disease modifying treatment options PIONEER data support AYVAKIT's efficacy as the first disease modifying agent, with safety data at 25 mg highlighting potential for long-term treatment Patient impact was reflected on multiple measures of symptom and QoL improvement On track to submit sNDAto FDA for Non-Advanced SM by the end of 2022 sNDA, supplemental new drug application.

CLINICAL PANEL Q&A Assistant Professor of Medicine Hematology Oncology University of Alabama School of Medicine Birmingham, Alabama Pioneer Investigator PANKITVACHHANI, MD Professor of Medicine Division of Allergy and Immunology Washington University St. Louis, Missouri H. JAMES WEDNER, MD Assistant Professor Head IFA Outpatient Clinic for Allergology Charité University Berlin, Germany Pioneer Investigator FRANK SIEBENHAAR, MD

INVESTOR DAY 2022 Not for promotional use Expanding patient impact with precision medicine leadership President, R&D FOUAD NAMOUNI, MD

INVESTOR DAY 2022 Not for promotional use Our proven research and development engine development candidates nominated breakthrough therapy designations success rate from IND to clinical POC 14 80% 5 years from IND to first approval FDA approved indications approved medicines ~4 25 61

INVESTOR DAY 2022 Not for promotional use wt-KIT, wild-type KIT. 62 Targeting areas of high medical need and scaled patient impact MAST CELL DISEASES LUNG CANCER BREAST CANCER CANCER IMMUNOTHERAPY AYVAKIT: KIT D816V BLU-263: KIT D816V Research: wt-KIT GAVRETO: RET BLU-945: EGFR BLU-701: EGFR BLU-525: EGFR BLU-451: EGFR ex20 BLU-222: CDK2 Research: undisclosed Research: MAP4K1 Research: undisclosed Multiple additional undisclosed research programs in areas of medical need

INVESTOR DAY 2022 Not for promotional use We will achieve R&D scale by leveraging our strengths 63 LEADING PRECISION MEDICINE RESEARCH PLATFORM ADVANCED TRANSLATIONAL MEDICINE APPROACHES CULTURE OF INNOVATION Scientific rigor and depth Scientific rigor and depth Urgency to help patients Urgency to help patients Efficient resource allocation Efficient resource allocation Pairing of kinase and targeted protein degradation platforms builds on our knowledge and experience Robust scientific capabilities enable effective and efficient clinical strategy in complex disease areas Our talented and committed team forms the foundation of our strongR&D infrastructure +

Transforming treatment of EGFRm lung cancer President, R&D FOUAD NAMOUNI, MD

INVESTOR DAY 2022 Not for promotional use 1. American Cancer Society. Key Statistics About Lung Cancer. https://www.cancer.org/cancer/lung-cancer/about/key-statistics .. 2. Approximate patient numbers covering major markets –US, EU4, UK, and Japan. 1. Excludes rare mutations including exon 20 insertions. Internal estimates adapted from Ramalingam, et al. NEJM, 2020; Decision Resources Group: NSCLC Forecast and Epidemiology; and Harrison Seminars in Cancer Biology, 2020. 65 Our progress in addressing the medical need in EGFRm NSCLC • Working toaddress medical needs in EGFR-driven NSCLC through rationalcombinations • Advancing multiple clinical candidates with best-in-class potential derived from our strong discovery capability • Leveraging our knowledge and experience in NSCLC to generate decision-making data that is informing our development strategy •Lung cancer is the leading cause of cancer death globally 1 •EGFR is one of the most common oncogenic drivers in lung cancer 1 •There are ~60,000 first-line EGFRm NSCLC patients in major markets 2 •Patients with the EGFR L858R driver mutation have poorer outcomes

INVESTOR DAY 2022 Not for promotional use Patients with EGFRm NSCLC have significant medical needs despite standard of care EGFRmNSCLCPROGRESSION ON TARGET EGFR RESISTANCE C797X, L718X, L792X, G796X, etc. OFF TARGET RESISTANCE MET, ALK, RET, KRAS, BRAF, CCNE1, etc. INCOMPLETE DRIVER INHIBITION Poorer outcomes for L858R versus ex19del Persistence of cells with driver mutation osimertinib 66

INVESTOR DAY 2022 Not for promotional use Poorer outcomes in EGFR L858R are associated with incomplete EGFR inhibition 67 21.4 mo ex19del OS ~42 mo PFS 14.4 mo L858R ~31 mo OSIMERTINIBOUTCOMES IN FLAURA 1L NSCLC 1 ex19delL858R osimertinib Complete EGFR inhibition Incomplete EGFR inhibition OSIMERTINIBINHIBITION OF EGFR CELL LINES 2 1. Soria NEJM 2014; Ramalingam NEJM 2020. 2. Cross et al., Cancer Dis, 2014. ex19del, exon 19 deletionmutation; mo, months; PFS, progression free survival; OS, overallsurvival.

INVESTOR DAY 2022 Not for promotional use Target coverage based on preclinical data; Ref: Riess2018 J ThoracOncol. 68 Our EGFR portfolio strategy is comprehensive and modular BLU-945 BLU-701/525 BLU-451 •More potent on L858R than ex19del •Covers EGFR T790M and C797S •Potent coverage of L858R and ex19del •Covers EGFR C797S 12% 9% 47% 32% ex19del L858R Exon 20 insertions Atypical EGFR G719X, L861Q, etc.

INVESTOR DAY 2022 Not for promotional use 69 BLU-945 dose escalation data in late-line patients Updated BLU-945 monotherapy dose escalation data show: – Differentiated safety with limitedwild-type-EGFR-related adverse events that were not dose limiting – Robust target ctDNAresponses leading to tumor shrinkage – No durability of benefit,likely due to late-line disease heterogeneity and off-target resistance There is a significant medical need in 1L EGFR L858R – In treatment-naïve patients, EGFRm NSCLC is mainly driven by activating EGFR mutations – Patients with EGFR L858R have poorer outcomes versus ex19delwith standard of care osimertinib – Preclinical data in 1L EGFR L858R model showed BLU-945 + osimertinibwas better than monotherapy – Minimal evidence of wild-type-EGFR-related toxicity for BLU-945 + osimertinibcombination in early dose escalation data Prioritizing development of BLU-945 + osimertinib in 1L EGFR L858R ctDNA, circulating tumor DNA.

INVESTOR DAY 2022 Not for promotional use Data cutoff date: September 13, 2022. BID, twice daily; C1D1, cycle 1 day 1; C1D15, cycle 1 day 15; DLT, dose-limited toxicity; LFT, liver function tests. PD, progressive disease; PR, partial response; RP2D, recommended phase 2 dose; SD, stable disease; VAF, variant allele fraction. 70 BLU-945 monotherapy dose escalation data support combination development EGFR C797S ctDNA CLEARANCETUMOR SHRINKAGE PD SD PR 20% 0% -40% -60% -20% -100 -50 0 50 100 200mg BLU-945 BID 300mg BLU-945 BID 250mg BLU-945 BID Percent change in C1D15 VAF over pre-treatment (C1D1) Baseline EGFR mutational profile (C1D1; F1LCDx) ex19del C797S* L858R C797S* ex19del T790M C797S L858R C797S* ex19del T790M C797S ex19del T790M C797S L858R T790M C797S L858R C797S* L858R C797S* L858R T790M C797S ex19del T790M C797S* ex19del T790M C797S* ex19del T790M C797S 200mg BLU-945 BID 300mg BLU-945 BID 250mg BLU-945 BID BLU-945 WAS GENERALLY WELL-TOLERATED •Minimal evidence of wild-type-EGFR- related toxicity •Reported DLTs were non-EGFR-related –LFT elevations, fatigue, nausea and vomiting

INVESTOR DAY 2022 Not for promotional use Data cutoff date: September 13, 2022. **RB1 and TP53 loss is evidence for likely histological transformation; OffinM. J ThoracOncol, 2019. 71 Significant off-target resistance limits opportunity for EGFR targeted therapy in 2L+ •Significant tumor heterogeneity detected at baseline in late-line patients with multiple off-target drivers of resistance •Increase in off-target drivers also detected at end-of-treatment in a subset of patients •Off-target resistance likely driving limited responses and poor durability despite robust EGFR inhibition seen by ctDNA •Optimization of EGFR pathway inhibition is likely to be more successful in front-line, in the absence of multiple resistance mechanisms BRAF CCND1 ERBB4 FGFR2 KRAS PDGFRA PDGFRB PIK3CA RB1+TP53* CCNE1 24% with multiple off-target drivers ctDNAANALYSIS DETECTED MULTIPLE OFF-TARGET DRIVERS

INVESTOR DAY 2022 Not for promotional use Data on file. IC50, half-maximal inhibitory concentration; WT, wild-type; wtEGFR, wild-type EGFR. 72 BLU-945’s unique selectivity profile enables a wide therapeutic index and more potent inhibition of L858R with or without on-target resistance 0 10 20 30 40 50 60 70 010203040506070 wtEGFR / L858R IC50 wtEGFR / ex19del IC50 2 nd gen TKIs More selective for L858R More selective for ex19del BLU-945 1 st gen TKIs 3 rd gen TKIs L858 R L 85 8R / C7 97 S L858R / T790 M L8 58 R / T 79 0M / C797S Ex19de l / T 79 0M / C 79 7 S 1 10 100 1000 BLU-945 osimertinib gefitinib

INVESTOR DAY 2022 Not for promotional use Tavera-Mendoza. EORTC-NCI-AACR, 2022. mOS, median overall survival; PDX, patient-derived xenograft model; SEM, standard error of the mean. 73 BLU-945 and osimertinibcombine to more completely inhibit EGFR and extend survival in treatment-naïve L858R preclinical models Treatment period Treatment Vehicle BLU-945 75mg/kg Osimertinib 5mg/kg BLU-945 75mg/kg + Osimertinib 5mg/kg mOS(days) 89 136 125 163 LUN439 PDX (treatment naïve L858R) p-value (vs osi) <0.0001 ns - 0.04

INVESTOR DAY 2022 Not for promotional use Early SYMPHONY trial dose escalation data show BLU-945 + osimertinib combination has been generally well-tolerated to date Data cutoff date: September 13, 2022. 74 BLU-945 + OSIMERTINIB 80 MG DOSE ESCALATION Patients with EGFRm NSCLC and >1 prior TKI BLU-945 QD + 80 MG OSIMERTINIBBLU-945 BID + 80 MG OSIMERTINIB 200 mg QD 100 mg BID 300 mg QD 150 mg BID 400 mg QD (recently opened) QD and BID dose escalation is ongoing Minimal evidence of wild-type-EGFR- related toxicity No DLTs reported to date Upon RP2D selection, plan to initiate expansion cohort in patients with 1L L858R

INVESTOR DAY 2022 Not for promotional use 75 Plan to prioritize BLU-525, with minimal disruption to overall EGFR portfolio timeline Phase 1 HARMONY trial dose escalation update • BLU-701 showed early evidence of activity at low doses • Drug metabolism pathway has limited dose escalation Plan to prioritize BLU-525 and deprioritize BLU-701 • Different chemical structure with different metabolism pathway • Similar EGFR mutational coverage • Improved kinomeselectivity • Improved CNS penetration Next steps: • Plan to submit IND to FDA for BLU-525 in Q1 2023 • Patients currently enrolled in the HARMONY trial will be able to continue treatment CNS, central nervous system.

INVESTOR DAY 2022 Not for promotional use BLU-451 escalation ongoing with early response in EGFR ex20ins patient 76 63 yoF with ex20ins NSCLC Prior therapies: •carbo/pemetrexed/pembro •CLN-081 (dc’dfor toxicity) •BDTX-189 (dc’dfor PD) Phase 1 CONCERTO trial dose escalation update •Currently enrolling 400mg QD •No DLTs reported to date •No treatment-related grade 3+ AEs reported to date A cycle is 21 days. Data cutoff date: October 11, 2022. AE, adverse event. Ex20ins, exon 20 insertion mutation. BLU-451 200 mg QD Only related AE is grade 1 rash Confirmed PR (-58%) Treatment ongoing in cycle 5 Baseline Week 6

INVESTOR DAY 2022 Not for promotional use 77 Our EGFR portfolio strategy is comprehensive and modular BLU-945 BLU-525 BLU-451 12% 9% 47% 32% ex19del L858R Exon 20 insertions Atypical EGFR G719X, L861Q, etc. + osimertinib 1L NSCLC with EGFR L858R •2L+ exon20 NSCLC •1L exon20 NSCLC + BLU-945 1L NSCLC with EGFRmut

INVESTOR DAY 2022 Not for promotional use Precision at Scale: Delivering improved outcomes for people withEGFR-mutant NSCLC 78 SOLVING MAJOR MEDICAL PROBLEMS Do we have a winning approach to improve outcomes for patients with EGFR-mutant NSCLC? 1 2 3 4 BLU-945 monotherapy was clinically active and showed adifferentiated safety profile. However, durability of response was limited due to frequent off-target drivers in 2L+ patients Pulling forward BLU-525, the backup compound for BLU-701, to bring the best candidate into development with minimal disruption to the overall timeline Encouraging early activity data from the BLU-451 dose escalation trial Prioritizing development of BLU-945 in combination with osimertinibin 1L L858R, based on exciting preclinical data and early clinical safety data

INVESTOR DAY 2022 Not for promotional use Research innovation at scale Chief Scientific Officer PERCY CARTER, PHD

INVESTOR DAY 2022 Not for promotional use 80 Blueprint’s Science Leadership Team ROB MEISSNER, PHD SVP, Chemical Sciences RACHEL ERLICH, PHD VP, Translational Medicine & Integrated Research TIM LABRANCHE, DVM, PHD VP, Preclinical Safety & Comparative Medicine STEVE MILLER, PHD VP, Precision Open Innovation RONDA RIPPLEY, PHD VP, Quantitative Pharmacology & Drug Safety JASON BRUBAKER, PHD VP, Medicinal Chemistry SCOTT RIBICH, PHD VP, Biology Drug Discovery LAKSHMI MUTHUSWAMY, PHD Director, Computational Biology & Bioinformatics

INVESTOR DAY 2022 Not for promotional use 81 Research at Blueprint Medicines Blueprint Talent + Integrated Platforms Blueprint Precision Medicine Research Portfolio Blueprint Clinical Portfolio KIT EGFR CDK •Support development and enhancement of three therapeutic areas •Lead the creation of new therapeutic opportunities Develop both our talent and platforms

INVESTOR DAY 2022 Not for promotional use 82 Research at Blueprint Medicines Blueprint Talent + Integrated Platforms Blueprint Precision Medicine Research Portfolio Blueprint Clinical Portfolio KIT EGFR CDK Externally Partnered Programs Bus. Dev. & Research Partnerships Augment our internal efforts with external partnerships in both research & development Bus. Dev., business development.

INVESTOR DAY 2022 Not for promotional use 83 We have a focused approach to portfolio construction At all stages, early to late, we progress programs that have: Defined Value Inflections Delineated data-driven decision points at all R&D stages Blueprint Edge Benefits from our focused approach to small molecule drug discovery Transformative Potential Provides meaningful benefit to patients with high medical need Precision Approach Well-defined patient identification strategy, compatible with real world

INVESTOR DAY 2022 Not for promotional use 84 Today’s update Blueprint Talent + Integrated Platforms Blueprint Precision Medicine Research Portfolio Blueprint Clinical Portfolio KIT EGFR CDK Wild-type KIT program Immuno-oncology collaboration with Roche EGFR Backup Candidate CDK2 program Targeted Protein Degradation Efforts

INVESTOR DAY 2022 Not for promotional use Target coverage based on preclinical data; Ref: Riess2018 J ThoracOncol. 85 Our EGFR portfolio has potential to address all known driver mutations and associated resistance mechanisms BLU-945 BLU-525 BLU-451 •More potent on L858R than ex19del •Covers EGFR T790M and C797S •Potent coverage of L858R and ex19del •Covers EGFR C797S 12% 9% 47% 32% ex19del L858R Exon 20 insertions Atypical EGFR G719X, L861Q, etc.

INVESTOR DAY 2022 Not for promotional use BLU-701BLU-525 Potency (IC 50 , nM) [WT-selectivity] Exon19Deletion (enzyme / cell pEGFRPC9) 0.5 [109x] / 1.3 [83x]0.9 [19x] / 1.2 [96x] Exon19Deletion C797S (cell pEGFRBa/F3 Ex19Del/CS) 1.8 [107x]9.5 [12x] L858R (enzyme / cell pEGFRBa/F3 LR) 2.6 [21] / 3.3[33x]1.6 [10x] / 4.2 [27x] L858R C797S (cell pEGFRBa/F3 LR/CS) 3.3 [33x]8.5 [14x] KinomeSelectivityS(10) @ 3 m M0.0600.015 Brain PenetrationRat IV infusion (Kpuu)0.981.3 86 BLU-525 is an improved brain penetrant, reversible EGFR inhibitor Key advantages of BLU-525 over BLU-701: – Differentiated chemical structure altered metabolic profile – Improved kinomeselectivity, but retains high potency and wild-type EGFR selectivity – Improved safety profile in non-GLP and GLP toxicology studies (rodent, non-rodent) GLP, good laboratory practice. nM, nanomolar; IV, intravenous; uM, micromolar. See also: L. Tavera-Mendoza et al. AACR-NCI-EORTC 2022, Barcelona, Spain, October 26–28.

INVESTOR DAY 2022 Not for promotional use 87 BLU-525 is an improved brain penetrant, reversible EGFR inhibitor Together, BLU-525 and BLU-945 will cover both common EGFR mutations and associated primary resistance mutations EGFR mutational coverage* GefitinibOsimertinibBLU-525BLU-945 BLU-525 + osimertinib BLU-945 + osimertinib BLU-525 + BLU-945 1L L858R 1L ex19del 2L L858R or ex19del /T790M 2L L858R or ex19del /C797S 3L L858R or ex19del /T790M/C797S 1G3G Next GenerationPotential Combinations * Based on biochemical IC 50 .. 3L, third line; 1G, first generation; 3G, third generation. IC 50 >50 nM IC 50 ≤10 nM

INVESTOR DAY 2022 Not for promotional use 88 Targeting cancer pathways vulnerable to CDK2 inhibition Precision Medicine Critical Role in Progression Ovarian Cancer (20%) Endometrial Carcinoma (11%) Lung Adenocarcinoma (5%) Gastric Cancer (11%) Esophageal Cancer (8%) Triple Negative Breast Cancer (11%) HR+ / HER2- Breast Cancer CCNE1+ SolidTumors * 1L combo & CDK4/6i Resistance Others No targeted therapies approved to address these mechanisms of disease or resistance Strong biological rationale with preclinical and/or clinical validation However, molecular selectivity has been challenging to achieve historically by others No targeted therapies approved to address these mechanisms of disease or resistance Strong biological rationale with preclinical and/or clinical validation However, molecular selectivity has been challenging to achieve historically by others *CCNE1 amplification frequency represented as percentage of total patient samples. Data from the National Cancer Institute's TheCancer Genome Atlas Program ( www.cancer.gov/tcga ). HR+/HER2-, hormone receptor-positive, HER2-negative. CDK-CYCLIN COMPLEXES REGULATE THE CELL CYCLE ABERRANT CYCLIN E (CCNE1) DRIVES CELL PROLIFERATION CDK4/6 Cyclin D CDK2 Cyclin E CDK2 Cyclin A CDK1 Cyclin A/B M G1 S G2 CELL DIVISION DNA SYNTHESIS

INVESTOR DAY 2022 Not for promotional use 89 BLU-222 is a highly potent and selective CDK2 inhibitor BLU-222 CELL pRb IC 50 (nM) 4.2 pLamin / pRb (CDK1/2) 84x ENZYME (1mM ATP) CDK2 IC 50 (nM) 2.6 CDK4/2 150x CDK6/2 105x CDK7/2 2,700x CDK9/2 2,300x S(10) 0.045 BLU-222 has excellent potency, CDK-family selectivity, and overall kinomeselectivity ADME and toxicology profiles are projected to enable clinical combination strategies Pre-clinical studies in CCNE1-amplified setting has been discussed, and work in pre-clinical breast cancer modeling will be disclosedat SABCS 2022 OVCAR3 Cell Cycle Profile ADME, absorption, distribution, metabolism, and excretion; CDX, cell-derived xenograft; sgNTC, single-guide RNA against nontargeting control; sgRb, single-guide RNA against Rb. SABCS, San Antonio Breast Cancer Symposium. For initial BLU-222 poster, see: Victoria Brown et al. AACR Annual Meeting, 2022. OVCAR3 CDX

INVESTOR DAY 2022 Not for promotional use CDK4/6i, CDK4/6 inhibitor. 90 Broad R&D effort to support ongoing development of BLU-222 Multiple dose cohorts* RP2D BLU-222 + ER antagonist (ER+/HER2-breast) BLU-222 + CDK4/6i + ER antagonist (ER+/HER2-breast) BLU-222 Monotherapy (CCNE1+ tumors) PHASE 2 EXPANSION (PLANNED) PHASE 1 DOSE ESCALATION (ENROLLING; UPDATE ON RESULTS IN 1H23) BLU-222 + Chemotherapy (CCNE1+ tumors) •Safety •Preliminary clinical activity •Patient selection strategy *Includes monotherapy and combination regimens BLU-222 Monotherapy (Other CCNE1+ tumors / Basket) TRANSLATIONAL MEDICINE COLLABORATION WITH MD ANDERSON (ONGOING; PLANNED FOR 3 YEARS) New biomarker hypotheses Rational Combinations Indication expansion

INVESTOR DAY 2022 Not for promotional use GIST, gastrointestinal stromal tumor; mMCAS, monoclonal mast cell activation syndrome. 91 Scientific leadership in KIT biology KIT BLU-263 IDRX-73 (BLU-654) KIT exon 13 inhibitor for KIT-driven GIST out-licensed to IDRx wt-KIT Research program for inflammatory mast cell disorders KIT D816V inhibitor FDA and EMA approved for advSMand PDGFRA D842V mutant GIST US & EU marketing applications planned for non-advSM Next-generation KIT D816V inhibitor in clinical development for SM & mMCAS

INVESTOR DAY 2022 Not for promotional use *See: J. Fricke, J. et al. Allergy 2020 , 75 , 423; note that point prevalence was estimated based on regional data (Fricke) and current populations **See: P. Kolkhir, et al. Nature Reviews: Disease Primers 2022 , 8 : 61; 92 Expanding our leadership in mast cell-mediated diseases Wild-type KIT plays a central role in mast cell survival, proliferation, and activation. Mast cells are primary effector cells in several allergic-inflammatory diseases, including both inducible and spontaneous chronic urticaria. Chronic Urticaria is a debilitating inflammatory skin disorder characterized by wheals (hives) Complications include swelling/hives in inopportune sites (mouth, airway, genitals) and anaphylaxis Sleep disruption, stress, & anxiety due to severe itching are major contributors to disease burden Chronic Urticaria statistics Total estimated point prevalence in the U.S.+EU* ~2M Patients with both wheals (hives) and angioedema** 37% Lifetime incidence* 1.4% Patients with poor disease control** 1/3

INVESTOR DAY 2022 Not for promotional use 93 Aim to discover best-in-class wild-type KIT inhibitors We have identified multiple examples of compounds meeting our target product profile Advanced candidates have safety and ADME profiles consistent with either single agent or combination therapy AttributeIdeal Candidate BLU8758 pKIT/ proliferation IC 50 < 10 nM pKIT IC 50 4 nM / 17 nM PDGFR / FLT3 selectivity> 50x / > 50x 700x/ >580x Kinase Selectivity; S(10)< 0.1 0.06 Drug/Drug InteractionsLow potential Low/Moderate Peripherally RestrictedKpuu < 0.1 Kpuu = 0.04 ADME, absorption, distribution, metabolism, and excretion.

INVESTOR DAY 2022 Not for promotional use 94 A strategic collaboration with the potential to transform the field of cancer immunotherapy Robust kinase research platform & development capabilities Cancer immunotherapy expertise, assets and infrastructure EXPLORE COMPELLING TARGETS • Goal: Explore a range of immunokinasetargets to advance cancer immunotherapy •Interrogate and validate with genetic and tool compound approaches ADVANCE THROUGH LEAD OPTIMIZATION •4 targets investigated focusing on distinct and complementary immune mechanisms DELIVERY OF TOP PROGRAMS • Achieved: 2 targets advanced through lead optimization to stage of Development Candidate (DC) •MAP4K1: DC achieved; first-in- patient anticipated 2023 •2 nd target: DC anticipated 2023 2016 2019 2022 In collaboration with Roche. Blueprint Medicines and Roche are conducting activities for up to two programs, including the program targeting MAP4K1. For one of the programs, Blueprint Medicines has U.S. commercial rights and Roche has ex-U.S. commercialization rights. For one of the programs, Roche has worldwide commercialization rights.

INVESTOR DAY 2022 Not for promotional use Degrader figure from Nalawansha& Crews, Cell Chemical Biology 2020 , 27 , 998 –1014. 95 Platform diversification expands our vision and impact KINASE MEDICINE DISCOVERY PLATFORM AGILE DEGRADER DISCOVERY PLATFORM + Internal investment provides flexibility across our portfolio Collaboration with Proteovant& VantAIintroduces expertise and expands reach Enhanced selectivity Success with challenging kinases Differentiated pharmacology EXPECTED BENEFITS OF INTRODUCING DEGRADERS Portfolio optionality

INVESTOR DAY 2022 Not for promotional use 96 Strategy: Leverage the Blueprint library Our initial approach prioritizes heterobifunctional degraders, which can capitalize both on existing proprietary chemical matter and known E3 ligases. BLUEPRINT KINASE INHIBITOR LIBRARY Select potent, selective, and drug-like ligands from the kinase inhibitor library Optimize target degradation using well-studied E3 ligases Optimize degrader properties, selectivity, and potency via linker POTENT, SELECTIVE HETEROBIFUNCTIONAL DEGRADER LIBRARY STRATEGY APPLIES TO BOTH INTERNAL PROGRAMS AND PROTEOVANT COLLABORATION LIBRARY STRATEGY APPLIES TO BOTH INTERNAL PROGRAMS AND PROTEOVANT COLLABORATION Target Binder E3 Ligase Recruiter

INVESTOR DAY 2022 Not for promotional use 97 Portfolio impact Early Example: Internal kinase program with family selectivity challenges (oncology) Exploratory work revealed a selectivity divergence in inhibitor vs degrader SAR, and ability to tune selectivity Impact: opportunistic program initiation Heterobifunctional degrader effort now initiating for high-value Paralog B High selectivity observed vs. two key family off-targets; broader selectivity studies to come This year, we have started five early degrader programs : three internal and two with Proteovant Blueprint Degrader 1 Blueprint Degrader 2 Blueprint Degrader 3 Paralog A DC 50 (Dmax) @ 6h 60nM (63%) 110nM (67%) >10 m M Paralog B DC 50 (Dmax) @ 6h >10 m M 30nM (82%) 37nM (86%) Profile A-Selective A/B-Dual B-Selective SAR, structure activity relationship.

INVESTOR DAY 2022 Not for promotional use 98 Expanding the research platform to increase innovation & productivity KINASE PLATFORM KINASE PLATFORM NEW PLATFORMS INTEGRATED PLATFORM CURRENT CAPABILITIES TARGETED PROTEIN DEGRADATION UNPARALLELED PRODUCTIVITY COMPLEMENTARY & SCALABLE NEW TARGET CLASSES LIBRARY & NEW TARGET DISCOVERY EXPANSION Consolidate precision medicine platforms with combination of internal and external innovation YESTERDAY TODAYFUTURE EXPANSION AIMS TO DOUBLE THE HISTORIC OUTPUT OF OUR DISCOVERY ENGINE BY 2025 EXPANSION AIMS TO DOUBLE THE HISTORIC OUTPUT OF OUR DISCOVERY ENGINE BY 2025

INVESTOR DAY 2022 Not for promotional use 99 Pre-clinical portfolio Hit ID and Hit-to-Lead Lead Optimization PreclinicalDevelopment BLU-525 MAP4K1 I/O Target #2 Collaboration with Undisclosed Undisclosed Wild-type KIT Undisclosed Multiple Inhibitors Precision Oncology Heme & Mast Cells Immuno- Oncology Multiple Degraders (two in collaboration) Collaboration with

INVESTOR DAY 2022 Not for promotional use Precision at Scale: Driving innovation for long-term growth 100 How will we leverage our expertise and infrastructure to drive continued innovation and long-term growth? SCALING INNOVATION 1 2 3 Creating synergies between our robust discovery, clinical and commercial capabilities to build an optimized portfolio Announcing a new program targeting wild-type KIT, which builds on ourknowledge of KIT and leadership position in mast cell disorders Leveraging our kinase discovery platform as a unique advantage to pursue targeted protein degradation

INVESTOR DAY 2022 Not for promotional use Scaling our leadership in precision medicine Chief Operating Officer CHRISTY ROSSI

INVESTOR DAY 2022 Not for promotional use 102 A clear portfolio strategy to achieve our 2027 vision LEAD WITH THE SCIENCE Patient needs Important targets Blueprint edge DIVERSIFY RISK Next-gen strategies Balance risk & return BUILD SCALE Target & disease leadership areas LEVERAGE PARTNERSHIPS Scientific, clinical & commercial partnerships

INVESTOR DAY 2022 Not for promotional use 103 Diversified EGFRm NSCLC portfolio with a compelling risk-return profile ASSET AND OPPORTUNITY DIVERSITY ENABLES: •Balanced risk profile •Attractive commercial opportunity •Scientific, clinical, and commercial economies of scale TECHNICAL RISK TECHNICAL RISK SIZE OF OPPORTUNITY SIZE OF OPPORTUNITY 1L all comer BLU-945+BLU-525 1L L858R BLU-945+osi 1L, 2L ex20ins BLU-451 2L+ all comer BLU-945+other EGFR PORTFOLIO IMPACT/RISK PROFILE TECHNICAL RISK SIZE OF OPPORTUNITY 1L all comer BLU-945+BLU-525 1L L858R BLU-945+osi 1L, 2L ex20ins BLU-451 2L+ all comer BLU-945+other EGFR PORTFOLIO IMPACT/RISK PROFILE = Prioritized = Deprioritized Osi, osimertinib.

INVESTOR DAY 2022 Not for promotional use 104 Strategic use of back-up and next-gen programs in high value opportunities BLU-701 BLU-525 BLU-263 AYVAKIT DEEP BIOLOGICAL INSIGHTS ENABLE NEXT-GENERATION PROGRAMS Goal: expand patient impact, disease area leadership and program lifecycle ROUTINE BACK-UP STRATEGIES ACROSS PORTFOLIO Goal: manage development risk at the program and portfolio levels EGFRmNSCLC BACK-UP PROGRAM EGFRmNSCLC DEPRIORITIZED SYSTEMIC MASTOCYTOSIS CORE PROGRAM SYSTEMIC MASTOCYTOSIS NEXT-GEN

INVESTOR DAY 2022 Not for promotional use We are leaders in systemic mastocytosis 105 ~540 patient years of SM clinical data 3 FDA breakthrough therapy designations 2 FDA and EMA approved indications* On track to submit sNDAto FDA for non-advanced SM by the end of 2022 EMA, European Medicines Authority. * AYVAKIT is FDA approved for the treatment of adults with unresectable or metastatic PDGFRA exon 18 mutant gastrointestinal stromal tumor (GIST) and adults with Advanced SM. AYVAKYT is EMA approved for adults with unresectable or metastatic PDGFRA D842V mutant GIST and adults with Advanced SM after at least one systemic therapy.

INVESTOR DAY 2022 Not for promotional use 106 Deep disease insights drive perspectives on medical needs ADVSM(5-10%) ADVSM(5-10%) NON-ADVSM(90-95%) NON-ADVSM(90-95%) •AVYAKIT is the standard of care •Areas for continued innovation: ‒Long term follow up and OS ‒Combination data SYSTEMIC MASTOCYTOSIS ~32K prevalent patients, with ~16K diagnosed and visible in claims in U.S. •PIONEER trial data demonstrate compelling benefit/risk profile •First mover advantage is significant •High bar for differentiation

INVESTOR DAY 2022 Not for promotional use Business development is a key lever in our portfolio strategy 107 Strategic Partnerships Strategic Partnerships Geographic Expansion Geographic Expansion Buy-Side Transactions Buy-Side Transactions Program Partnerships Program Partnerships FOP, fibrodysplasiaossificans progressiva; I/O, immunotherapy; WW, worldwide. 2015: Discovery collaboration on FOP 2016: Global I/O research collaboration 2019: WW out-license of BLU-782 for FOP 2020: Global collaboration of GAVRETO ® 2018: Greater China partnering on 3 clinical programs 2021: Greater China partnering on 2 preclinical programs 2021: Acquisition for its EGFR Exon20 program 2022: Research collaboration on targeted protein degradation 2022: Supply agreement for osimertinib 2021: Translational research collaboration on CDK2 2021: Distribution agreement for AYVAKIT T® in Israel 2022: Distribution agreement for AYVAKIT TM in 14 Central Eastern European countries >$1.1B of capital brought in to-date inclusive of upfront, milestones and royalties 2022: WW out-license of BLU-654 for GIST

INVESTOR DAY 2022 Not for promotional use Our portfolio to deliver Precision at Scale 108 LUNG CANCER PORTFOLIO BLU-222 AREA PDGFRA GIST RET-altered cancers Advanced SM Non-Advanced SM EGFRm NSCLC CDK2 vulnerable breast & other cancers GLOBAL TAMs PRODUCTS ~250,000+ patients 4+ marketed products by the end of 2027 Includes TAMs for AYVAKIT based on potential approval in Non-Advanced SM and other investigational therapies based on potential future approvals in other target indications.

INVESTOR DAY 2022 Not for promotional use Anticipated near-term milestones 109 PROGRAMAREA OF FOCUSMILESTONETIMING AYVAKIT Non-Advanced SM Submit sNDAto FDAQ4 2022 Present full registrational data from PIONEER trialQ4 2022 / Q1 2023 BLU-263Report top-line 12-week Part 1 data from HARBOR trialQ4 2022 BLU-525 EGFRm NSCLC Submit IND to FDAQ1 2023 BLU-451Report BLU-451 dose escalation data1H 2023 BLU-222CDK2-vulnerable cancersReport BLU-222 dose escalation data1H 2023

INVESTOR DAY 2022 Not for promotional use 110 Expanding AYVAKIT to treat patients with non-advanced SM to realize a compelling near- term growth opportunity Tackling important medical problems representing significant opportunities in lung, breast and other cancers Building on proven research track record to broaden theopportunities we can pursue to drive long-term growth Precision at Scale: key themes from today’s presentation EXPANDING PATIENT IMPACT SOLVING MAJOR MEDICAL PROBLEMS SCALING INNOVATION

KATE HAVILAND Chief Executive Officer

INVESTOR DAY 2022 Not for promotional use 112 “2027 Blueprint” strategy -double our impact, in half the time Approved medicines Disease leadership areas Late-stage clinical programs Research platforms Cumulative development candidates 2011-2022 2 1 2 1 14 Planned 2022-2027 4+ 3+ 4+ 2 25+ 2027